The invention relates to 2-(2-amino-2-thiazolin-4-yl)acetic acid or its pharmaceutically acceptable acid addition or cationic salts, as well as its lower alkyl esters, useful in detoxification of certain metal ions in animals, including humans.
In recent years there has been a growing awareness of the importance of trace metals in the environment, many of which are essential to nutrition at appropriate levels but give rise to toxic manifestations if the animal body is exposed to higher levels. The role of chelating agents in medicine (chelation therapy) to remove excessive quantities of metal ions which are producing toxic effects has been reviewed recently by Williams and Halstead, J. Toxicol.: Clin. Toxicol., 19(10), 1081-1115 (1983).
Metals are unique poisons in that they are not subject to metabolic destruction such as occurs for organic poisons. Examples of metals which are essential for nutrition at low levels but toxic in excessive amounts include chromium, cobalt, copper, iron, manganese, molybdenum, selenium and zinc. Less commonly encountered toxic metal ions are those of aluminum, antimony, arsenic, beryllium, nickel, tellurium, thallium and tin, as well as certain radioactive elements. Of course, chelation therapy can also be employed to reduce toxic levels of heavy metals, for example, lead, mercury and cadmium. Chelation therapy is a method of treatment of animals, including humans, which reduces toxic levels of one or more metal ions to a level at which the metal ion is innocuous by administration of one or more chelating agents. Effective chelation therapy depends upon selection of the appropriate chelating agent or combination of such agents, commonly referred to in the art as "ligands". While a number of ligands are known to be useful in chelation therapy, the search for new useful ligands continues.
2-Amino-2-thiazoline has been reported to be useful in protecting animals from exposure to radioactivity, Chem. Abstr. 92, 209061q (1980), see also British Pat. No. 1,109,150.
2-Aminothiazol-4-acetic acid is an important intermediate for preparation of certain beta-lactam antibiotics, especially cephalosporins. See, e.g., European Patent Appln. No. 34,340.